Synthesis, Docking and Cytotoxicity Evaluation of N-(5-(Benzyl- Thio)-1,3,4-Thiadiazol-2-yl)-2-(3-Methoxyphenyl)Acetamide Derivatives as Tyrosine Kinase Inhibitors With Potential Anticancer Activity

Ahmad Mohammadi-Farani; Tayebeh Bahrami; Alireza Aliabadi

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Synthesis, Docking and Cytotoxicity Evaluation of N-(5-(Benzyl- Thio)-1,3,4-Thiadiazol-2-yl)-2-(3-Methoxyphenyl)Acetamide Derivatives as Tyrosine Kinase Inhibitors With Potential Anticancer Activity

Author(s):

Ahmad Mohammadi-Farani^{1, 2},

Tayebeh Bahrami^{3, 4},

Alireza Aliabadi^{1, 4,*}

1Novel Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

2Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

3Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

4Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

Journal of Reports in Pharmaceutical Sciences:Vol. 3, issue 2; 159-168

Published online:Aug 30, 2014

Article type:Research Article

Received:Jul 28, 2014

Accepted:Aug 20, 2014

How to Cite:Ahmad Mohammadi-FaraniTayebeh BahramiAlireza AliabadiSynthesis, Docking and Cytotoxicity Evaluation of N-(5-(Benzyl- Thio)-1,3,4-Thiadiazol-2-yl)-2-(3-Methoxyphenyl)Acetamide Derivatives as Tyrosine Kinase Inhibitors With Potential Anticancer Activity.J Rep Pharm Sci.3(2):e147699.

Abstract

In the recent years, targeted therapy of the neoplastic diseases is a current strategy used by oncologists. Hence, design and discovery of novel targeted anticancer therapeutics is an interesting topic in the current research of medicinal chemistry. A new series of 1,3,4- thiadiazole derivatives were prepared and their anticancer activity was assessed against PC3, SKNMC and HT29 cell lines by application of the MTT assay. Compound 3e with para positioning of the methoxy moiety demonstrated the highest inhibitory potency against PC3 (IC50 = 22.19 ± 2.1 μM) and SKNMC (IC50 = 5.41 ± 0.35 μM) cell lines in this series. This compound rendered a superior cytotoxic activity than imatinib. Compound 3f with ortho positioning of the fluorine displayed the most cytotoxic activity against HT29 cell line compared to other tested derivatives (IC50 = 12.57 ± 0.6 μM). Molecular docking studies on Abl as well as Src tyrosine kinases were also performed and potential hydrogen bindings were observed for ligand-receptor interaction.

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